One of the major objectives of this study is to clarify the immunopathologic events and the contributing factors in demyelinating diseases such as experimental allergic encephalomyelitis (EAE) and multiple sclerosis (MS), in an attempt to bring together an increasing well-defined experimental model and an important human disease. One proposal involves the study of immunologic responses to myelin basic protein (BP) identified as the inducing antigen in EAE. Inasmuch as the amino acid sequence of the basic protein is known, it is now possible to investigate the determinants responsible for various immunologic activities of the protein such as the capacity to induce disease, elicit hypersensitive cells and antibody, and provide protection from disease. Monkeys will be used to study certain pathologic features and immunologic treatments, as EAE in this species bears a unique resemblance to MS in humans. Although myelin BP induces EAE, it does not appear to elicit the demyelinating factor found in the sera of whole CNS-sensitized rodents and primates (resembling a similar factor observed in acute MS). A search will be undertaken to identify the central nervous system (CNS) component responsible for this activity using cultured myelinated CNS tissue. In addition to these fundamental studies designed to develop the usefulness of EAE as a model for human demyelinating disease, two objectives directly involve MS. The detection of early myelin loss could provide a powerful diagnostic tool. Recent technical improvements using insoluble radio-labeled immunoglobulins make it feasible to undertake the development of a sensitive test to detect myelin components such as BP in the spinal fluid or serum of affected subjects. Another important aspect of this project will be devoted to examining the immunologic response to cells from patients to BP and other CNS components. Certain viruses which have come into recent prominence as agents associated with MS or slow infections affecting CNS myelin will be used in these tests to clarify their role as possible initiating agents in an autoallergic syndrome. The examination of patients' cells for allergic responses may significantly contribute to the development of diagnostic and therapeutic aids.